Dexlansoprazole acts as a proton pump inhibitor (PPI) having actions such as a gastric acid secretion suppressive action or a gastric mucosal protective action, and has been widely used as a therapeutic agent for peptic ulcers, and the like.
However, the dexlansoprazole is poorly soluble in water and very unstable in acids, and thus is easily decomposed in gastric juice, which is an acidic solution. Further, pH affects the stability of dexlansoprazole in an aqueous solution state. Accordingly, for effective in vivo delivery of dexlansoprazole through oral administration, there is a need for a dosage form in which dissolution characteristics in the upper small intestine portion are improved while the loss of activity caused by gastric juice is minimized by enteric coating.
Thus, in the related art, a method for manufacturing a pharmaceutical formulation by coating a pharmaceutical formulation in a dosage form of a granule, pellet, tablet, or capsule with an enteric material or using a capsule comprising an enteric material has been used.
For example, Patent Document 1 (US 2011/0189271 A1) discloses a pharmaceutical formulation comprising: (a) a pharmacologically inert core; (b) a drug layer surrounding the core and comprising dexlansoprazole, or a salt thereof, and one or more pharmaceutically acceptable excipients; (c) an intermediate layer surrounding the drug layer; and (d) an enteric layer surrounding the intermediate layer. In this case, Patent Document 1 discloses that the dexlansoprazole or the salt thereof is amorphous, and the pharmaceutical formation may be formulated in a dosage form of a tablet or capsule.
In addition, Patent Document 1 describes a method for preparing the pharmaceutical formulation, comprising: (a) combining dexlansoprazole, a metal compound, and one or more pharmaceutically acceptable excipients with a solvent, to prepare a dexlansoprazole solution; (b) spraying the dexlansoprazole solution obtained in (a) onto a pharmacologically inert core; (c) spraying an intermediate layer onto the drug-coated core obtained in (b); and (d) spraying an enteric coating layer onto the intermediate layer-coated core obtained in (c).
Referring to the examples described in the above document, methods of processing a pharmaceutical formulation comprising dexlansoprazole into a pellet form through various steps and formulating the pharmaceutical formulation in the pellet form into a dosage form of a tablet or capsule are disclosed. However, according to the method, the amorphous raw material is recrystallized, so that the drug cannot be released as pure amorphous dexlansoprazole. In addition, when a tablet is prepared by using dexlansoprazole processed into the pellet form as in Patent Document 1, hardness may deteriorate or the disintegration time may be delayed, and friability is high, so that a problem in that the stability of the tablet deteriorates may also occur, and as the production process becomes complicated, there is a disadvantage in that the production efficiency deteriorates.